Clinical Trials /

Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin

NCT03258554

Description:

This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab or cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin
  • Official Title: Randomized Phase II/III Trial of Radiotherapy With Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy With Concurrent Cetuximab in Patients With Locoregionally Advanced Head and Neck Cancer With a Contraindication to Cisplatin

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01522
  • SECONDARY ID: NCI-2017-01522
  • SECONDARY ID: NRG-HN004
  • SECONDARY ID: NRG-HN004
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03258554

Conditions

  • Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Head and Neck Squamous Cell Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Squamous Cell Carcinoma of Unknown Primary
  • Stage III Hypopharyngeal Carcinoma AJCC v8
  • Stage III Laryngeal Cancer AJCC v8
  • Stage III Lip and Oral Cavity Cancer AJCC v8
  • Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • Stage IVA Hypopharyngeal Carcinoma AJCC v8
  • Stage IVA Laryngeal Cancer AJCC v8
  • Stage IVA Lip and Oral Cavity Cancer AJCC v8
  • Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • Stage IVB Hypopharyngeal Carcinoma AJCC v8
  • Stage IVB Laryngeal Cancer AJCC v8
  • Stage IVB Lip and Oral Cavity Cancer AJCC v8
  • Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Interventions

DrugSynonymsArms
CetuximabCetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225Arm I (cetuximab, radiation therapy)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm II (durvalumab, radiation therapy)

Purpose

This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab or cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1
      therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and
      neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the
      hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS)
      compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally
      advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis
      that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard
      therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have
      a contraindication to cisplatin. (Phase III)

      SECONDARY OBJECTIVES:

      I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and
      Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy
      versus RT/cetuximab.

      II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors
      that overexpress PD-L1.

      III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron
      emission tomography [PET]-computed tomography [CT]), locoregional failure, distant
      metastasis, and competing mortality in the two arms by known risk factors, including p16
      status and omega score.

      IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in
      the physical function domain of European Organization for Research and Treatment of Cancer
      Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to
      12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally
      advanced HNC who have a contraindication to cisplatin.

      V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT)
      will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson
      Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline
      to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically
      unfit for cisplatin.

      VI. To compare swallowing related performance and function short and long term using the
      Performance Status Scale for Head & Neck Cancer Patients (PSS-HN).

      VII. To evaluate gastrostomy tube retention rates between arms.

      EXPLORATORY OBJECTIVES:

      I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the
      adaptive immune response using three types of immunophenotyping compared to radiation
      combined with cetuximab.

      II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end
      of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.

      III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24
      months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI
      (subscales) between arms in patients with locoregionally advanced HNC who have a
      contraindication to cisplatin.

      IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and
      PRO-CTCAE.

      V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.

      VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the
      European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment
      repeats every week for up to 8 cycles in the absence of disease progression or unacceptable
      toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated
      radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.

      ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every
      4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
      Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

      After completion of study treatment, patients are followed up at 1 month, every 4 months for
      1 year, every 6 months for 2 years, then annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (cetuximab, radiation therapy)Active ComparatorPatients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.
  • Cetuximab
Arm II (durvalumab, radiation therapy)ExperimentalPatients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA

          -  Patients must have pathologically confirmed, previously untreated, unresected squamous
             cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of
             unknown head/neck primary prior to step 1 registration; submission of hematoxylin and
             eosin (H&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue
             block (or punch biopsy of FFPE block) to the biospecimen bank at University of
             California, San Francisco (UCSF) for central review for oropharyngeal and unknown
             primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory
             for all patients; investigators should check with their pathology department regarding
             release of biospecimens before approaching patients about participation in the trial;
             for oropharyngeal and unknown primaries, submission of H&E and p16 stained slides
             (with the required block for PD-L1) to the biospecimen bank at UCSF for central review
             is also required prior to step 2 registration

               -  Note: fine needle aspirates (FNA) samples are not acceptable since they do not
                  provide enough material for PD-L1 and p16 testing; however, if a cell block
                  derived from the FNA is available, it is allowable if there are sufficient cells
                  present in the block for PD-L1 testing; Dr. Jordan will determine this upon
                  receipt; for sites submitting FNA cell blocks for ALL patients they must do so
                  within 7-10 business days from registering the patient; sites must confirm with
                  their cytology/pathology labs to make sure they can provide the required material
                  as the bank must be able to retain these samples for the mandatory testing

          -  Patients must have locoregionally advanced head and neck squamous cell carcinoma
             (HNSCC)

               -  For p16-positive oropharyngeal/unknown primaries, American Joint Committee on
                  Cancer [AJCC] 8th edition stage III and selected stage I-II based on smoking
                  status in pack-years

               -  For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative
                  oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB

               -  Based on the following minimum diagnostic workup within 60 days prior to step 1
                  registration:

                    -  General history and physical examination by a radiation oncologist or
                       medical oncologist or ear, nose and throat (ENT) or head & neck surgeon

                    -  For larynx, hypopharynx, and base of tongue primaries, a
                       laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is
                       required, unless the patient cannot tolerate or refuses

               -  Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI)
                  (with contrast, unless contraindicated) or PET/CT; note that the CT portion of
                  the PET/CT must be of diagnostic quality, including contrast administration
                  unless contraindicated. If the CT portion of the PET/CT study is low-dose
                  (non-diagnostic), then an additional CT or MRI study with contrast (unless
                  contraindicated) is required

               -  Chest imaging: chest CT with and without contrast (unless contraindicated) or
                  PET/CT

          -  Patients must have a contraindication to cisplatin as defined in the following bullet
             points; sites must complete the online tool at comogram.org prior to step 1
             registration to determine if the patient is eligible; the scores must be recorded on a
             case report form (CRF)

               -  Age >= 70 with moderate to severe comorbidity or vulnerability to cisplatin,
                  defined as having one or more of the following conditions within 30 days prior to
                  step 1 registration:

                    -  Modified Charlson Comorbidity Index >= 1

                    -  Adult Comorbidity Evaluation (ACE)-27 Index >= 1

                    -  Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score <
                       0.80

                    -  Geriatric screening (G-8) score =< 14

                    -  Cancer and Aging Research Group (CARG) toxicity score >= 30%

                    -  Cumulative Illness Rating scale for Geriatrics (CIRS-G) score >= 4 OR

               -  Age < 70 with severe comorbidity or vulnerability to cisplatin, defined as having
                  two or more of the following conditions within 30 days prior to step 1
                  registration

                    -  Modified Charlson Comorbidity Index >= 1

                    -  ACE-27 Index >= 1

                    -  GCE omega PFS-score < 0.80

                    -  G-8 score =< 14

                    -  CARG Toxicity score >= 30%

                    -  CIRS-G score >= 4 OR

               -  Age >= 18 with an absolute or relative contraindication to cisplatin, defined as
                  one or more of the following within 30 days prior to step 1 registration:

                    -  Creatinine clearance (CC) > 30 and < 60 cc/min; for this calculation, use
                       the Cockcroft-Gault formula

                    -  Zubrod performance status 2 prior to step 1 registration

                    -  Pre-existing peripheral neuropathy grade >= 1

                    -  History of hearing loss, defined as either:

                         -  Existing need of a hearing aid OR

                         -  >= 25 decibel shift over 2 contiguous frequencies on a pretreatment
                            hearing test as clinically indicated

          -  Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 14 days prior to step 1
             registration)

          -  Platelets >= 100,000 cells/mm^3 (within 14 days prior to step 1 registration)

          -  Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve
             hemoglobin [Hgb] >= 9.0 g/dl is acceptable) (within 14 days prior to step 1
             registration)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times
             institutional upper limit of normal (within 14 days prior to step 1 registration)

          -  Serum bilirubin =< 1.5 x institutional upper limit of normal (within 14 days prior to
             step 1 registration)

          -  Measured creatinine clearance (CL) > 30 mL/min or calculated creatinine CL > 30 mL/min
             by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine
             collection for determination of creatinine clearance (within 14 days prior to step 1
             registration)

          -  For women of childbearing potential, a negative serum or urine pregnancy test within
             14 days prior to step 1 registration; Note: women will be considered post-menopausal
             if they have been amenorrheic for 12 months without an alternative medical cause; the
             following age-specific requirements apply:

               -  Women < 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy)

               -  Women >= 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses > 1 year ago, had
                  chemotherapy-induced menopause with last menses > 1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy)

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to step 1 registration

          -  PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA

          -  For patients with oropharyngeal or unknown primaries: p16 determination by
             immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and
             cytoplasmic staining of tumor cells), confirmed by central pathology review

               -  Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries,
                  analysis of p16 status prior to step 2 registration/randomization is not required
                  (p16 status will be analyzed centrally post-hoc); step 2 registration for these
                  patients can be completed after step 1 registration

        Exclusion Criteria:

          -  PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA

          -  Prior invasive malignancy within the past 3 years (except for non-melanomatous skin
             cancer, and early stage treated prostate cancer); synchronous head and neck primaries
             are ineligible

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

               -  Note: Prior external beam radiotherapy is excluded, but iodine 131 is allowed

          -  Prior immunotherapy

          -  Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy,
             or immune therapy for the study cancer

          -  Major surgery within 28 days prior to step 1 registration

          -  Proven evidence of distant metastases

          -  If both of the following conditions are present, the patient is ineligible:

               -  =< 10 pack-year smoking history

               -  p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1
                  (AJCC 8th Edition)

                    -  Note: in the event that a registered patient with =< 10 pack-years has a
                       p16-positive result on central review with the tumor and nodal stage T0-3,
                       N0-1 (AJCC 8th Edition), then the site will be notified that the patient is
                       ineligible

          -  Zubrod performance status >= 3

          -  Body weight =< 30 kg

          -  Patients with oral cavity cancer are excluded from participation if the patient is
             medically operable and resection of the primary tumor is considered technically
             feasible by an oral or head and neck cancers surgical subspecialist;(please consult
             the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine
             [MD], if clarification is needed on an individual case)

          -  Sodium < 130 mmol/L or > 155 mmol/L (within 14 days of step 1 registration, unless
             corrected prior to step 1 registration)

          -  Potassium < 3.5 mmol/L or > 6 mmol/L (within 14 days of step 1 registration, unless
             corrected prior to step 1 registration)

          -  Fasting glucose < 40 mg/dl or > 400 mg/dl (within 14 days of step 1 registration,
             unless corrected prior to step 1 registration)

          -  Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl (within 14
             days of step 1 registration, unless corrected prior to step 1 registration)

          -  Magnesium < 0.9 mg/dl or > 3 mg/dl (within 14 days of step 1 registration, unless
             corrected prior to step 1 registration)

          -  Unstable angina and/or congestive heart failure requiring hospitalization within 3
             months prior to step 1 registration

          -  Transmural myocardial infarction within 3 months prior to step 1 registration

          -  Respiratory illness requiring hospitalization at the time of step 1 registration

               -  Note: if the respiratory illness is resolved and the patient meets the
                  eligibility status above, then the patient can be considered for the trial

          -  Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires
             oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1
             registration

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis

          -  Clinically apparent jaundice and/or known coagulation defects

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc.])

               -  The following are exceptions to this criterion:

                    -  Patients with vitiligo or alopecia;

                    -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                       hormone replacement;

                    -  Any chronic skin condition that does not require systemic therapy;

                    -  Patients without active disease in the last 5 years may be included but only
                       after consultation with the medical oncology study chair;

                    -  Patients with celiac disease controlled by diet alone

          -  History of active primary immunodeficiency including, but not limited to acquired
             immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and
             Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not
             required for entry into this protocol; the need to exclude patients with AIDS from
             this protocol is necessary because the treatment involved in this protocol may be
             immunosuppressive; patients with known HIV, CD4 counts >= 200/uL, and undetectable
             viral loads who are stable on an antiretroviral regimen may be included

          -  Current or prior use of immunosuppressive medication within 14 days before step 1
             registration, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid

          -  Receipt of live attenuated vaccination within 30 days prior to step 1 registration

          -  Medical or psychiatric illness which would compromise the patient's ability to
             tolerate treatment or limit compliance with study requirements

          -  Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception during treatment and
             for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this
             exclusion is necessary because the treatment involved in this study may be
             significantly teratogenic; women who are breastfeeding are also excluded

          -  Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or
             any of study drug excipients

          -  History of allogenic organ transplantation

          -  Uncontrolled hypertension

          -  Uncontrolled cardiac arrhythmia

          -  Uncontrolled serious chronic gastrointestinal condition associated with diarrhea

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and tuberculosis [TB] testing
             in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
             surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV
             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence
             of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV])
             antibody are eligible only if polymerase chain reaction is negative for HCV
             ribonucleic acid (RNA)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT) defined as the occurrence of an adverse event (AE) during the specified observation window (Lead -in)
Time Frame:Up to 4 weeks after radiation therapy (RT)
Safety Issue:
Description:AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Locoregional failure (LRF)
Time Frame:From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer or unknown causes, assessed up to 3 years
Safety Issue:
Description:LRF will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.
Measure:Distant metastasis (DM)
Time Frame:From randomization until first evidence of distant metastasis, assessed up to 3 years
Safety Issue:
Description:DM will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.
Measure:Competing mortality
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated by cumulative incidence methods and the effects of other covariates will be assessed using the Generalized Competing Event Model for Cancer Risk model.
Measure:Response on 4-month fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT)
Time Frame:Up to 4 months
Safety Issue:
Description:Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST). Response rates between the two arms will be compared using Fisher's exact test.
Measure:Acute toxicity
Time Frame:Up to 180 days after the end of radiation therapy
Safety Issue:
Description:The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
Measure:Late toxicity
Time Frame:Up to 3 years
Safety Issue:
Description:Late toxicities > 180 days after the end of radiation therapy. The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
Measure:Change in quality of life (QOL) analysis
Time Frame:Baseline up to 12 months
Safety Issue:
Description:Assessed using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ)/Head-and-Neck module (H&N35), EuroQol- 5 Dimension (EQ5D), M. D. Anderson Dysphagia Inventory (MDADI), patient reported outcomes (PRO)-CTCAE, geriatric screening (G8). The mean summary score of the EORTC QLQ/H&N35, EQ5D, MDADI, PRO-CTCAE, G8, CCI, and the subscales will be determined. The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
Measure:Change in swallowing QOL using total composite M. D. Anderson Dysphagia Inventory (MDADI) score
Time Frame:Baseline up to 1 year
Safety Issue:
Description:The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.
Measure:Translational research, including PD-L1 and p16
Time Frame:Up to 3 years
Safety Issue:
Description:Analyses of interaction between treatment arm and marker status will be done. Additionally toxicity for the two arms by marker status will be compared. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS. Potential covariates evaluated for the multivariate models would be assigned treatment, age, Zubrod performance status, T-stage, N-stage, primary site, smoking history, other risk factors, as well as p16 and/PD-L1.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

January 27, 2020